Enhanced immune capture of extracellular vesicles with gelatin nanoparticles and acoustic mixing.

Extracellular vesicles (EVs) originating from cancer cells incorporate various critical biomolecules that can aid in early cancer diagnosis. However, the rapid analysis of these micro vesicles remains challenging due to their nano-scale size and overlapping dimensions, hindering sufficient capture in terms of quantity and purity. In this study, an acoustofluidic device was developed to enhance the yield of immune-captured EVs. The channel of the device was modified with degradable gelatin nanoparticles (∼220 nm) to increase the surface roughness, and subsequently treated with CD63 antibodies. The acoustic-induced streaming would prolong the rotation time of the EVs in the targeted continuous flow area, improving their aggregation towards the surrounding pillars and subsequent capture by the specific CD63 antibodies. Consequently, the capture efficiency of the device was improved when the signal was on, as evidenced by enhanced fluorescence intensity in the main channel. It is demonstrated that the acoustofluidic device could enhance the immune capture of EVs through acoustic mixing, showcasing great potential in the rapid and fast detection of EVs in liquid biopsy applications.

RETINAL VASCULAR OCCLUSION AND COVID-19 DIAGNOSIS: A Multicenter Population-Based Study.

BACKGROUND: Several ocular diseases have been reported in patients with coronavirus disease 2019 (COVID-19), especially retinal vascular occlusion. This study aimed to examine the risk of retinal vascular occlusion after COVID-19 diagnosis. METHODS: This retrospective cohort study was based on 46 health care organizations in the United States using the TriNetX network. Individuals who had laboratory confirmation of COVID-19 from January 1, 2020, to December 31, 2021, were included. Multivariate analysis was adjusted on age, sex, race, and comorbidities, and hazard ratio was calculated using the Cox proportional hazard regression model. RESULTS: A total of 1,460,634 paired individuals were enrolled for analysis. Patients with COVID-19 had a significantly higher risk of branch retinal vein occlusion (hazard ratio 1.27, 95% confidence interval [CI] 1.04-1.52) than those without COVID-19. The cumulative incidence rate of branch retinal vein occlusion was also significantly higher in patients with COVID-19 compared with those without COVID-19 (log-rank P = 0.014). Within 12 weeks after COVID-19 diagnosis, the transient effect of central retinal vein occlusion (hazard ratio 1.59, 95% confidence interval 1.15-2.17) and branch retinal vein occlusion (hazard ratio 2.11, 95% confidence interval 1.51-2.95) were observed. CONCLUSION: This large-scale multicenter study demonstrated that retinal vein occlusion may be associated with COVID-19.

The risk assessment of uveitis after COVID-19 diagnosis: A multicenter population-based study.

Reports on uveitis after COVID-19 have been limited. Our objective was to examine the risk of uveitis among COVID-19 patients. This was a retrospective cohort study based on the TriNetX platform. The exposure group was patients with positive laboratory test result for SARS-CoV-2 and the comparison group was those tested negative for COVID-19 throughout the study period. The endpoint is the new diagnoses of uveitis. This study composed of 2 105 424 patients diagnosed with COVID-19 (55.4% female; 62.5% white; mean age at index 40.7 years) and 2 105 424 patients (55.4% female; 62.4% white; mean age at index 40.7 years) who never had COVID-19. There was significantly increased risk of new diagnosis of uveitis since the first month after diagnosis of COVID-19 compared with matched controls (HR: 1.18, 95% CI: 1.03-1.34) up to 24 months (HR: 1.16, 95% CI: 1.09-1.22). Our findings strengthen those previously raised by case series with a larger and multicenter study. We found that uveitis was significantly associated with COVID-19 infection. Our findings reiterate the need for careful investigation as well as increased awareness from ophthalmologists in considering the possibility of COVID-19 in vulnerable patients with new presentation of uveitis.

Comparative study of coronary artery bypass grafting combined with off-pump mitral valvuloplasty versus coronary artery bypass grafting alone in patients with moderate ischemic mitral regurgitation.

INTRODUCTION: Whether mitral surgery should be performed simultaneously with coronary artery bypass grafting (CABG) in patients with moderate ischemic mitral regurgitation (MIMR) is controversial. This study was performed to introduce a method of off-pump mitral valvuloplasty after off-pump CABG (OPCABG) and compare it with OPCABG alone. METHODS: Eighty-three patients with MIMR underwent OPCABG. Among them, 21 patients (Group A) underwent posterior mitral annuloplasty without cardiopulmonary bypass, and 62 patients (Group B) underwent OPCABG alone. The primary endpoint of follow-up was the mitral regurgitation area. RESULTS: The mean mitral regurgitant area in Group A and B was 6.42 ± 1.02 and 5.49 ± 1.24 cm2 preoperatively (p = .479), 2.93 ± 1.35 and 3.28 ± 1.93 cm2 at 1 week postoperatively (p = .516), 3.06 ± 2.16 and 3.09 ± 1.85 cm2 at 3 months postoperatively (p = .839), and 3.02 ± 1.60 and 3.7 cm2 (median) at 1 year postoperatively (p = .043). There was less regurgitation in Group A at the mid-term. Intragroup comparison showed significant differences between the preoperative and postoperative values in both groups, with no difference in the regurgitant area at each postoperative time point in Group A but a significant difference between 3 months and 1 year postoperatively in Group B (p = .042). Multiple linear regression showed that the mid-term mitral regurgitant area changes were negatively correlated with graft flow and positively correlated with age. CONCLUSION: In patients with MIMR who underwent OPCABG plus off-pump mitral valve annuloplasty, the mitral regurgitant area was smaller and mitral regurgitation recurrence was less frequent at the mid-term follow-up.

Distal end side-to-side anastomosis of sequential coronary bypass for size mismatched saphenous vein grafts and coronary arteries.

INTRODUCTION: The distal end anastomosis is critical to the entire sequential grafts in coronary artery bypass grafting (CABG), but caliber mismatch diminishes the quality of the anastomosis. We aimed to introduce a modified distal end side-to-side (deSTS) anastomosis to handle the size mismatch and compared with classic distal end end-to-side (deETS) anastomosis. METHODS: From January 2014 to December 2018, 185 patients who underwent off-pump CABG with size mismatched sequential vein grafts (≥3.5 mm) and target coronaries (1.0-1.5 mm) at the distal end anastomoses were included. We retrospectively reviewed the data of the patients, perioperative and follow-up outcomes were analyzed. RESULTS: The deSTS group (n = 67) showed higher anastomotic flow (19.8 ± 8.0 vs 14.9±6.8 mL/min; p < 0.001) and lower pulsatility index (2.7 ± 0.8 vs 3.2 ± 1.0; p = 0.001) than the deETS group (n = 118). Higher incidence of in-hospital myocardial infarction (MI) was found in the deETS group but without significant difference (9.0% vs. 15.3%; p = 0.220). Kaplan-Meier analysis illustrated a relatively lower MI and major adverse cardiovascular and cerebrovascular events (MACCE) incidence in the deSTS group, and the deSTS group was associated with a reduction in long-term death, MI and MACCE in the adjusted Cox regression model. In addition, relatively higher graft patency was found in the deSTS group. CONCLUSIONS: The deSTS anastomosis showed superiority in solving size mismatch in sequential CABG, including better intraoperative flow dynamics, ideal long-term graft patency and reduced the incidence of perioperative and follow-up adverse events especially in MI.

Aging Characteristics and Ecological Effects of Primary Microplastics in Cosmetic Products Under Different Aging Processes.

Microplastics are becoming an increasingly environmental concern, but only a few studies have focused on primary microplastics. Herein, four primary microplastics (Lapis, Jade, Topaz and White) commonly used in cosmetic products were selected to investigate the effects of sunlight, seawater, and soil aging on their environmental behaviors. After sunlight and seawater aging, the surfaces of all four microplastics developed breaks and cracks, with particle sizes decreased and specific surface areas increased. Topaz exhibited the most significant changes under sunlight and seawater aging and its maximum adsorption capacity of phenanthrene significantly increased by 22.50% and 47.86%, respectively. Under soil aging, amending with either White or Topaz changed the soil bacterial community composition and diversity, but they had less ecological impacts than polyvinyl chloride plastic. The results of this study provide vital information for understanding the aging characteristics, environmental behavior, and ecological effects of primary microplastics under natural aging processes.

A clinical study of genetic testing to guide the dosing of warfarin after heart valve replacement.

OBJECTIVE: To explore the role of genetic testing of VKORC1 and CYP2C9 in determining the dosage of warfarin after aortic valve replacement. METHODS: A total of 172 patients receiving warfarin after aortic valve replacement were divided into a control group (n = 86) and an experimental (n = 86) group based on acceptance of genetic testing. In the experimental group, three loci of VKORC1 and CYP2C9 were tested by polymerase chain reaction-restriction fragment length polymorphism technique, and the initial dose of warfarin was determined based on the genetic testing results and warfarin oral-dose table recommended by U.S. Food and Drug Administration (FDA). In the control group, warfarin (3 mg per night) was used as the initial dose. The international normalized ratio (INR) of each patient was continuously monitored after medication. The percentages of patients meeting the target INR in the two groups at specific time points and at 3-month follow-up after discharge from the hospital were monitored, and the incidence of various adverse events was compared between the groups. RESULTS: Based on the results of genetic testing, 68 patients received 3-4 mg/d (79.1%), 10 patients received 0.5-2 mg/d (11.6%), and eight patients received 5-7 mg/d (9.3%) as the initial dosages of warfarin in the experimental group. The percentages of the patients meeting the target INR on the third and sixth day of postoperative medication were 45.3% and 73.3%, respectively, in the experimental group, and 29.8% and 58.3%, respectively, in the control group. The INR critical values during hospitalization occurred in 2.3% in the experimental group and in 7.1% in the control group, while the percentage of the patients meeting the target INR after 3 months was 86.1% in the experimental group and 83.1% in the control group. CONCLUSION: Genetic testing may guide the selection of the initial dose of warfarin after heart valve replacement to rapidly achieve a stable dose.

Novel Cardioplegia Delivery in Patients with Severe Aortic Regurgitation.

During aortic valve replacement (AVR) in patients with severe aortic regurgitation (AR), repeated delivery of cardioplegia into the coronary ostia using a routine infusion cannula may induce coronary ostial injury. This study aims to introduce a new no-touch delivery method with reduced time and similar or better outcomes. Preliminary results have shown that no-touch cardioplegia delivery method was a simple, safe, and effective approach for cardioplegia infusion during AVR in patients with severe AR.

MiR-140-5p upregulation suppressed ß-glycerophosphate-induced vascular smooth muscle cell calcification via targeting TLR4.

BACKGROUND: The role and function of microRNA (miRNA, miR)-140-5p in the calcification of vascular smooth muscle cells (VSMCs) have been explored in this study. METHODS: The calcium nodules formed in transfected and ß-glycerophosphate (ß-GP)-treated VSMCs were observed using Alizarin Red S staining, and alkaline phosphatase (ALP) activity was determined. VSMC apoptosis was detected with flow cytometry assay. The target gene of miR-140-5p was predicted and confirmed with dual-luciferase reporter assay. Relative expressions of miR-140-5p, toll like receptor 4 (TLR4) and vascular calcification-related proteins (α-smooth muscle actin, α-SMA; Msh Homeobox 2, MSX2; bone morphogenetic protein 2, BMP2; Kruppel-like factor 4, KLF4; Runt-related transcription factor 2, RUNX2) were measured through quantitative real time polymerase chain reaction (qRT-PCR) and western blot. RESULTS: MiR-140-5p upregulation reversed the effects of ß-GP on downregulating miR-140-5p and α-SMA expressions, enhancing ALP activity, calcium nodule formation and cell apoptosis, and upregulating levels of MSX2, BMP2, KLF4 and RUNX2. TLR4 was the target of miR-140-5p, and offset the effects of miR-140-5p on ß-GP-induced VSMCs. CONCLUSIONS: MiR-140-5p upregulation represses ß-GP-induced calcification of VSMCs via targeting TLR4, providing a potential therapeutic method for vascular calcification.

Genetic Variations of Ionotropic Glutamate Receptor Pathways on Interferon-α-induced Depression in Patients with Hepatitis C Viral Infection.

IMPORTANCE: The most supportive evidence of the inflammation theory of depression is that up to one-third of patients with Hepatitis C virus infection (HCV) develop clinical depressive episodes during interferon-α (IFN-α) therapy. As glutamate-mediated excitotoxicity has been found to be a consequence of excessive inflammation and a pathogenic mechanism of depression, it is plausible to investigate genes on ionotropic glutamate receptor pathways. OBJECTIVE: To identify the at-risk genetic variations on ionotropic glutamate receptor pathways for interferon-α-induced depression. METHOD: We assessed 291 patients with chronic HCV undergoing IFN-α therapy and analyzed the single nucleotide polymorphisms (SNPs) in genes related to ionotropic glutamate receptors in this prospective case-control study. Patients who developed IFN-α-induced depression anytime during the treatment were defined as the case group, while those who did not were defined as the control group. Genomic DNA was extracted from peripheral blood and analyzed by Affymetrix TWB array. Allelic and haplotype association tests were conducted using χ2 tests to assess the difference in allele and haplotype frequencies between cases and controls. Additionally, we performed 5000 permutations to control gene-wide family-wise error rates and create empirical p-values. Stratified analyses were then done to control for confounders and adjust odds ratios for our significant SNPs. We also did an additional stratified analysis to re-assess genes with near-significant SNPs (empirical p-value=0.05-0.10), employing Bonferroni correction with the effective number of independent tests to control gene-wide family-wise error rates. RESULTS: The minor and major allele frequencies of rs7542 (empirical p-value=0.0310) in MAPK3, rs3026685 (empirical p-value=0.0378) in PICK1, rs56005409 (empirical p-value=0.0332) in PRKCA, rs12914792 (empirical p-value=0.0096), rs17245773 (empirical p-value=0.0340) in RASGRF1, and rs78387863 (empirical p-value=0.0086), rs74365480 (empirical p-value=0.0200) in RASGRF2 were found significantly different between cases and controls. Haplotype association tests also revealed one significant haplotype in PRKCA (empirical p-value=0.0200) and one in RASGRF1 (empirical p-value=0.0048). Stratified analyses showed no signs of confounders for most of our significant SNPs, except for rs78387863 in RASGRF2. After a re-assessment of our near-significant genes by stratified analyses, two SNPs in GRIN2B turned significant. CONCLUSIONS: This study provided supportive evidence of the involvement of the RAS/RAF/mitogen-activated protein kinase (MAPK) signaling pathway and glutamate ionotropic receptor AMPA type subunit 2(GluR2) transportation in the pathogenesis of IFN-α-induced depression.

Does Bilateral Internal Mammary Artery Grafting Better Suit Patients With Diabetes?　- Two Different Ways to Explore Outcomes.

BACKGROUND: This analysis compared short-term mortality, sternal wound infection (SWI), and long-term survival outcomes in diabetic patients who underwent coronary artery bypass grafting (CABG) with bilateral (BIMA) vs. single (SIMA) internal mammary artery, as well as in diabetic vs. non-diabetic patients undergoing BIMA grafting.Methods and Results:Nineteen studies were included in the study, covering 21,143 different patients. Of these patients, 6,464 underwent CABG with BIMA, 10,264 underwent CAGB with SIMA, 11,584 had diabetes, and 6,717 did not. Compared with SIMA, BIMA had a significantly lower risk of in-hospital mortality (odds ratio [OR] 0.73, P=0.02), but a significantly higher risk of SWI (OR 1.30, P=0.04). However, compared with non-diabetic patients who underwent CABG with BIMA, diabetic patients with BIMA grafting did not have significantly higher risks of either mortality (OR 1.22, P=0.53) or SWI (OR 1.10, P=0.72). No significant differences were detected with different harvesting techniques. Longer term, BIMA was associated with a significantly higher rate of survival than SIMA (hazard ratio [HR] 0.76, P<0.001). CONCLUSIONS: Results from the 2 types of comparisons indicate that BIMA is a preferable option for diabetic patients, even though it has a higher risk of infection. CABG with BIMA is also associated with a long-term survival benefit.

[Comparison of pedicled and scheltoned endoscopic methods harvesting saphenous vein in shank].

OBJECTIVE: To compare the efficacies of endoscopic harvesting saphenous vein as sequential graft by pedicled and scheltoned technique. METHODS: From June 2013 to December 2013, a total of 93 patients undergoing coronary artery bypass with endoscopic vein harvesting in shank were recruited. Saphenous veins were harvested by pedicled method in group A (n =46) and scheltoned method in group B (n =47). Harvesting method was decided by a random number for each patient. Saphenous veins were used as sequential grafts during off-pump coronary artery bypass. Inter-group comparisons were made in time for harvesting, time for repairing, venous injuries and perioperative effect of saphenous vein. The postoperative follow-up period was 30 days. Early failure of saphenous vein graft was evaluated with coronary computed tomography (CT) angiography. RESULTS: All saphenous veins in shank were harvested successfully. No significant difference existed in vein length. In groups A and B, average time for harvesting was (21. 7 ± 5. 6) and (27. 4 ± 6. 4) min (P < 0. 05) and time for repairing (7. 2 ± 2. 7) and (10. 6± 4. 4) min respectively (P <0. 05). No severe injury resulted in non-using of saphenous in both groups. The repair rates of saphenous vein were 10. 9% and 38. 3% respectively (P < 0. 05). For each repaired saphenous vein, the average number of locations was (1. 6 ± 0. 5) and (3. 1 ± 1. 0) sites respectively (P < 0. 05). All patients were discharged uneventfully. There was no perioperative onset of myocardial infarction or malignant arrhythmia. For groups A and B, 89. 1% and 93. 6% were followed up for 1 month post-operation. No angina, myocardial infarction or heart failure occurred. For groups A and B, 32 and 37 cases were re-examined on CT coronary angiography and all saphenous vein grafts maintained patency. CONCLUSIONS: Pedicled method is more safe and reliable for endoscopic saphenous vein harvesting. It can ensure the quality of sequential graft, shorten harvesting time and reduce the risks of vein injury.

Off-pump anteroapical aneurysm plication following left ventricular postinfarction aneurysm: effect on cardiac function, clinical status and survival.

BACKGROUND: In patients with coronary disease and aneurysm, ventricular reconstruction with revascularization is a surgical option. Details of patient selection and optimal surgical technique are still debated. We report our results with off-pump aneurysm plication after ventricular aneurysm with relative wall thinning. METHODS: We retrospectively reviewed the records of 248 patients who had an operation for postinfarction left ventricular aneurysm. Reconstruction was accomplished by off-pump anteroapical aneurysm plication. The following variables were recorded: preoperative clinical, angiographic and echocardiographic findings and operative procedures. Outcomes were early mortality, long-term survival and poor 5-year result, defined as the need for transplantation or repeated hospitalization for congestive heart failure. Risk factors were pinpointed using the t test and survival curves. Independent risk factors were identified using Cox regression methods. RESULTS: Hospital mortality was low (2.0%). Mean follow-up was 5.8 (standard deviation [SD] 3.8) years. Actuarial survival at 1 and 5 years was 94% and 84%. Among the 232 survivors, 200 were in functional class I or II, and the average increase in ejection fraction was 14.0% (SD 3.1%). As determined by multivariable analysis, factors predicting poor outcome were advanced age, ejection fraction less than 0.35, conicity index less than 1, end-systolic volume index greater than 80 mL/m2, advanced New York Heart Association functional class and congestive heart failure. CONCLUSION: Using wall thinning as a criterion for patient selection, the technique of off-pump anteroapical aneurysm plication can be performed with low operative mortality and provides good symptomatic relief and long-term survival.

Utilization of Pulsatile flow to Decellularize the Human Umbilical Arteries to Make Small-Caliber Blood Vessel Scaffolds.

PURPOSE: To explore the effect of pulsatile flow in the decellularization process of small blood vessels. METHODS: A total of 30 human umbilical cords were used in the current study. The umbilical cords were flushed with 0.25% trypsin/0.01% EDTA for 30 minutes, followed by treatment with 1% sodium dodecyl sulfate sodium dodecyl sulfate for 3 hours. The effectiveness of decellularization on the umbilical artery wall was analyzed by mechanical analysis. The scaffolds' biocompatibility was observed by co-culture with the human umbilical endothelial cells. RESULTS: The maximum stress of the arteries before and after denuding was 3.55 ± 0.42N and 3.50 ± 0.43N, respectively. Under the pressure of 300 mmHg, 28 pieces of umbilical cords remained intact before and after the flushing, while 2 pieces ruptured under 300 mmHg. There was no significant difference in mechanical properties between flushed and control arteries. Isolated human umbilical endothelial cells grow and spread well on the decellularized umbilical artery scaffolds. CONCLUSIONS: Decellularization by pulsatile flow in human umbilical artery is a convenient, rapid and efficient approach to increase the availability of small caliber blood vessel scaffolds. KEY WORDS: Decellularization; Human umbilical artery; Scaffolds; Small diameter blood vessel; Vascular tissue engineering.

Transcription factor GATA1 represses oxidized-low density lipoprotein-induced pyroptosis of human coronary artery endothelial cells.

BACKGROUND: Atherosclerosis (AS) is defined as a chronic inflammatory disorder underly the pathogenesis of cardiovascular diseases (CVDs). Endothelial pyroptosis is associated with AS-like diseases and other CVDs. OBJECTIVE: This work was designed to expound on the effect of GATA-binding protein 1 (GATA1) on pyroptosis of human coronary artery endothelial cells (HCAECs) in AS. METHODS: HCAECs were treated with oxidized-low density lipoprotein (ox-LDL) to establish HCAEC injury models. Plasmids for overexpressing GATA1 or silencing retinoic acid-related orphan receptor α (RORα) were transfected into HCAECs. Thereafter, the mRNA levels of GATA1 and RORα in HCAECs were detected using real-time quantitative polymerase chain reaction. HCAEC viability was examined using the cell counting kit-8 method. The levels of pyroptosis-related proteins NOD-like receptor protein 3 (NLRP3), cleaved-Caspase-1, N-terminal of gasdermin D (GSDMD-N), and pyroptosis-related inflammatory cytokines interleukin (IL)-1ß and IL-18 were determined using Western blot and enzyme-linked immunosorbent assays, respectively. The targeting relationship between GATA1 and RORα was verified using the chromatin-immunoprecipitation assay. Then, the rescue experiment was conducted to explore the effect of RORα on pyroptosis of ox-LDL-treated HCAECs. RESULTS: In ox-LDL-treated HCAECs, GATA1 and RORα expressions were decreased, HCAEC viability was reduced, and the levels of NLRP3, cleaved-Caspase1, GSDMD-N, IL-1ß, and IL-18 were elevated. GATA1 overexpression increased HCAEC viability and attenuated pyroptosis. GATA1 bound to the RORα promoter region to stimulate RORα transcription, and RORα suppression facilitated ox-LDL-induced pyroptosis of HCAECs. CONCLUSIONS: GATA1 activated RORα transcription and therefore limited pyroptosis of ox-LDL-treated HCAECs.

Strong association of lumbar disk herniation with diabetes mellitus: a 12-year nationwide retrospective cohort study.

Background: Despite reports on the association between diabetes mellitus (DM) and lumbar disk herniation (LDH), large-scale, nationwide studies exploring this relationship are lacking. We aimed to examine the profiles of DM in individuals with LDH and explore the potential mechanisms underlying the development of these disorders. Methods: This retrospective, population-based study was conducted between 2008 and 2019 using data from the National Health Insurance (NHI) research database in Taiwan. The primary outcome was the date of initial LDH diagnosis, death, withdrawal from the NHI program, or end of the study period. Results: In total, 2,662,930 individuals with and 16,922,546 individuals without DM were included in this study; 719,068 matched pairs were established following propensity score matching (1:1 ratio) for sex, age, comorbidities, smoking, alcohol consumption, antihyperglycemic medications, and index year. The adjusted risk for developing LDH was 2.33-fold (95% confidence interval: 2.29-2.37; P<0.001), age-stratified analysis revealed a significantly greater risk of LDH in every age group, and both males and females were approximately twice as likely to develop LDH in the DM compared with non-DM cohort. Individuals with DM and comorbidities had a significantly higher risk of developing LDH than those without, and the serial models yielded consistent results. Treatment with metformin, sulfonylureas, meglitinides, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, or alpha-glucosidase inhibitors was associated with a more than 4-fold increased risk of LDH in the DM cohort. DM was strongly associated with the long-term development of LDH; over the 12-year follow-up period, the cumulative risk of LDH was significantly higher in patients with than without DM (log-rank P<0.001). Conclusion: DM is associated with an increased risk of LDH, and advanced DM may indicate a higher risk of LDH.

A chronological review of COVID-19 case fatality rate and its secular trend and investigation of all-cause mortality and hospitalization during the Delta and Omicron waves in the United States: a retrospective cohort study.

Introduction: Coronavirus disease 2019 (COVID-19) has caused more than 690 million deaths worldwide. Different results concerning the death rates of the Delta and Omicron variants have been recorded. We aimed to assess the secular trend of case fatality rate (CFR), identify risk factors associated with mortality following COVID-19 diagnosis, and investigate the risks of mortality and hospitalization during Delta and Omicron waves in the United States. Methods: This study assessed 2,857,925 individuals diagnosed with COVID-19 in the United States from January 2020, to June 2022. The inclusion criterion was the presence of COVID-19 diagnostic codes in electronic medical record or a positive laboratory test of the SARS-CoV-2. Statistical analysis was bifurcated into two components, longitudinal analysis and comparative analysis. To assess the discrepancies in hospitalization and mortality rates for COVID-19, we identified the prevailing periods for the Delta and Omicron variants. Results: Longitudinal analysis demonstrated four sharp surges in the number of deaths and CFR. The CFR was persistently higher in males and older age. The CFR of Black and White remained higher than Asians since January 2022. In comparative analysis, the adjusted hazard ratios for all-cause mortality and hospitalization were higher in Delta wave compared to the Omicron wave. Risk of all-cause mortality was found to be greater 14-30 days after a COVID-19 diagnosis, while the likelihood of hospitalization was higher in the first 14 days following a COVID-19 diagnosis in Delta wave compared with Omicron wave. Kaplan-Meier analysis revealed the cumulative probability of mortality was approximately 2-fold on day 30 in Delta than in Omicron cases (log-rank p < 0.001). The mortality risk ratio between the Delta and Omicron variants was 1.671 (95% Cl 1.615-1.729, log-rank p < 0.001). Delta also had a significantly increased mortality risk over Omicron in all age groups. The CFR of people aged above 80 years was extremely high as 17.33%. Conclusion: Male sex and age seemed to be strong and independent risk factors of mortality in COVID-19. The Delta variant appears to cause more hospitalization and death than the Omicron variant.

Risk assessment of retinal vascular occlusion after COVID-19 vaccination.

Coronavirus disease 2019 (COVID-19) vaccines are associated with several ocular manifestations. Emerging evidence has been reported; however, the causality between the two is debatable. We aimed to investigate the risk of retinal vascular occlusion after COVID-19 vaccination. This retrospective cohort study used the TriNetX global network and included individuals vaccinated with COVID-19 vaccines between January 2020 and December 2022. We excluded individuals with a history of retinal vascular occlusion or those who used any systemic medication that could potentially affect blood coagulation prior to vaccination. To compare the risk of retinal vascular occlusion, we employed multivariable-adjusted Cox proportional hazards models after performing a 1:1 propensity score matching between the vaccinated and unvaccinated cohorts. Individuals with COVID-19 vaccination had a higher risk of all forms of retinal vascular occlusion in 2 years after vaccination, with an overall hazard ratio of 2.19 (95% confidence interval 2.00-2.39). The cumulative incidence of retinal vascular occlusion was significantly higher in the vaccinated cohort compared to the unvaccinated cohort, 2 years and 12 weeks after vaccination. The risk of retinal vascular occlusion significantly increased during the first 2 weeks after vaccination and persisted for 12 weeks. Additionally, individuals with first and second dose of BNT162b2 and mRNA-1273 had significantly increased risk of retinal vascular occlusion 2 years following vaccination, while no disparity was detected between brand and dose of vaccines. This large multicenter study strengthens the findings of previous cases. Retinal vascular occlusion may not be a coincidental finding after COVID-19 vaccination.

The risk of ischemic stroke significantly increases in individuals with blepharitis: A population-based study involving 424,161 patients.

INTRODUCTION: To investigate the association of blepharitis and ischemic stroke. METHODS: This nationwide retrospective cohort study used population-based data in Taiwan. Individuals aged 20 and above with diagnosis of blepharitis was included based on electrical medical records. After exclusion of ineligible cases, 424,161 patients were identified between 2008 and 2018. The blepharitis and non-blepharitis cohorts were matched based on sex, age, and comorbidities. Multivariable-adjusted Cox proportional hazards model was adopted to calculate the hazard ratio and 95% confidence interval (CI) between blepharitis and non-blepharitis cohorts. The incidence of ischemic stroke was estimated by Kaplan-Meier analysis. RESULTS: 424,161 pairs of blepharitis cohort and non-blepharitis cohort were 1:1 propensity score matched for statistical analysis. Patients with blepharitis had significantly increased risk of ischemic stroke compared with the individuals without blepharitis (adjusted hazard ratio 1.32, 95% CI 1.29-1.34, P < 0.001). A significantly higher risk of ischemic stroke was observed in blepharitis cohort with a previous diagnosis of cancer than in those without cancer (P for interaction < 0.0001). Kaplan-Meier survival analysis revealed the cumulative incidence of ischemic stroke increased in the blepharitis cohort compared with that in the non-blepharitis cohort in 10 years (log-rank P < 0.001). The follow-up period analysis further indicated 1.41-fold adjusted hazard (95% CI 1.35-1.46, P < 0.001) of ischemic stroke within a year after blepharitis diagnosis. CONCLUSIONS: Patients with blepharitis had an elevated risk of developing ischemic stroke. Early treatment and active surveillance are suggested for patients with chronic blepharitis. Further research is required to determine the casual relationship between blepharitis and ischemic stroke, as well as the underlying mechanism.